Topical ethanol is used as a dermal penetration enhancer in some commercial products. Previous studies have demonstrated that chronic ethanol consumption can also disrupt skin barrier function, leading to increased transdermal penetration. This observation becomes much more relevant if a single drinking episode induces similar changes. The purpose of this study was thus to examine the transdermal penetration of three model chemicals after acute ethanol consumption. Wistar rats were gavaged with either 10, 6, 4.3, 3, 1.5 g/kg ethanol or saline and allowed to recover for 2 or 24 h. Blood and skin ethanol levels were determined and in vitro penetration experiments performed. The herbicide paraquat, industrial solvent N,N-dimethylformamide (DMF), and insect repellent N,N-diethyl-m-toluamide (DEET) were used as is model chemicals. Absorption was determined and directly compared between ethanol- and saline-treated skin by calculating enhancement ratios. Blood ethanol levels range from 0.25 to 0.015% at 2 h with skin levels at 12–18% of blood values. Ethanol enhances the absorption of paraquat, DMF, and DEET in a dose-dependent fashion. Paraquat and DEET showed no appreciable reduction in enhancement between 2 and 24 h postgavage for the 10-g/kg dose, but DMF did. Enhancement ratios were higher at 24 h for 10 than for 6 g/kg animals, demonstrating a dose-response relationship for recovery time. These studies imply that increased absorption of topical chemical occurs after alcohol ingestion. Both acute and chronic ethanol consumption can compromise the dermal barrier.